The Kissler laboratory is intent on unraveling the function of the many genes associated with autoimmune disease. The laboratory’s focus is on type 1 diabetes. However, a significant number of the more than 50 genes associated with autoimmune diabetes have in fact been implicated in multiple autoimmune disorders, and these genes are the targets of the lab’s research because their broad association with autoimmunity indicates that they may have a very fundamental impact on immune tolerance.

The particular expertise of the laboratory lies in the generation of gene knockdown mice within the nonobese diabetic (NOD) mouse model for type 1 diabetes. Using lentiviral transgenesis, the lab generates mice in which target genes are silenced by RNAi in a doxycycline-inducible manner. This approach allows the manipulation of gene expression at any given time during immune development or disease onset. The Kissler lab thereby seeks to define the functional contribution to disease of genes implicated in human autoimmunity.

These investigations will serve two purposes. First, many of these autoimmunity genes have not been functionally characterized previously. Studying these genes will provide new knowledge on their biological function and define their role in immune tolerance. Second, by characterizing those pathways that most critically modulate the risk of autoimmunity, new therapeutic strategies can be devised to prevent or halt the autoimmune attack that underlies type 1 diabetes and the many other autoimmune disorders that affect up to 8% of the population.